Synthesis and Characterization of PEG-Iron Oxide Core-Shell Nanoparticles for Dual Hyperthermia and Chemotherapy Treatment of Cancer

Synthesis and Characterization of PEG-Iron Oxide Core-shell Nanoparticles for Dual Hyperthermia and Chemotherapy Treatment of Cancer

Robert J. Wydra¹, Anastasia M. Kruse¹, Younsoo Bae², Kimberly W. Anderson¹, J. Zach Hilt¹

¹Department of Chemical and Materials Engineering, University of Kentucky

²Department of Pharmaceutical Sciences, University of Kentucky

Hyperthermia, the heating of tissue in the 41-45°C range, can induce cellular death on its own or work in conjunction with chemotherapy for improved cancer therapy [1].  In this study, core-shell nanocomposites were prepared with the intent of co-delivery of a chemotherapeutic (Geldanamycin and 17-N-Allylamino-17-demethoxygeldanamycin) and heat.  The core-shell nanoparticles were prepared using atomic transfer radical polymerization (ATRP) to coat iron oxide (Fe₃O₄) nanoparticles with a poly(ethylene glycol) (PEG) based  polymer shell.  The iron oxide core allows for the remote heating of the particles in an alternating magnetic field (AMF).  Nanoparticle mediated thermal therapy feasibility was demonstrated in vitro with a thermoablation (55°C) study on A549 lung carcinoma cells.  Combinational therapy of chemotherapeutic and hyperthermia on A549 was investigated to demonstrate an enhanced therapeutic effect.

FTIR measurements verified the PEG coating by observing peaks at 1715cm^-1 and 1105cm^-1, which represent the carbonyl group (C=O) and ether group (C-O-C), respectively.  TGA indicated different mass loss profiles and slight differences in overall mass loss between the core citrate coated particles and the polymer coated particles.   The results from thermal therapy demonstration indicated that there is no toxic effect from the AMF coil or particles in solution over the timeframe of the experiment.  When the particles were exposed to the AMF field, there was complete cellular death as a result of the heat generate by the nanoparticles.

ATRP was successfully utilized to coat iron oxide nanoparticles with a PEG based polymer shell.  For the time frame of the thermal therapy experiments, there is a minimal toxic effect observed in A549 cells for the 10 mg/ml concentration of PEG-coated Fe₃O₄ nanoparticles.  Thermoablation of A549 demonstrates the potential use of polymer coated particles for thermal therapy.  Future work involves the refinement of the dual therapy study to demonstrate a synergistic effect of a co-delivery of chemotherapeutics and hyperthermia from magnetic nanoparticles.

References:

[1] Issels RD. Eur J Cancer. 2008:44:2546-2554.